The Cytotoxic Cell Studies Group has made significant advances in our study of the murine Ly49 gene family. We have demonstrated significant differences in gene number and organization of the Ly49 genes in 129/J mice as compared to B6 mice. This provides an interesting parallel to the variation in gene content between individuals found for the analogous class I receptor gene family (KIRs) in humans. We have prepared a sequence-ready contig map of over 30 BACs from the 129/J strain. This work has been published in Genomics (Vol. 79, pages 437-444) The analysis of Ly49 cDNAs from liver NK cells lead to the identification of an additional upstream promoter that is active only in bone marrow and liver-derived NK cells. This finding provides a useful foundation for studies on the activation of Ly49 genes during development. This work has been published in The Journal of Immunology (Vol. 168, pages 5163-5169). Our current studies are focussed on the analysis of a putative stochastic switch element that we have discovered. We have generated transgenic C57BL/6 mice containing the 129/J Ly49o gene for our studies on the generation of the Ly49 repertoire, and we are in the process of generating 129/J mice lacking the entire Ly49 gene cluster. These mice will allow us to investigate the role this gene family plays in the regulation of the immune response.